ABCG - ATP Binding Cassette Subfamily G | Elisa - Clia - Antibody - Protein

Background

The ABCG subfamily is part of the ATP-binding cassette (ABC) transporter superfamily, which utilizes the energy from ATP hydrolysis to transport various molecules across cellular membranes. ABCG transporters are unique because they function as half-transporters and must dimerize (either as homodimers or heterodimers) to become functional. They play crucial roles in lipid transport, cholesterol homeostasis, and drug resistance.ABCG group plays a crucial role in the controlled transport of hydrophobic compounds across cellular membranes. In humans, five members of the ABCG family have been identified. The primary substrates for at least four of the ABCG members are both endogenous and dietary lipids, with ABCG1 specifically involved in cholesterol transport. ABCG2, on the other hand, exhibits a much broader substrate specificity. Its capability to transport a diverse range of pharmaceuticals positions it as one of the multidrug-resistant ABC transporters expressed in humans.

Protein Structure

ABCG transporters have distinctive structural features:

• Transmembrane Domains (TMDs): Each ABCG transporter has six transmembrane helices that form the pathway for substrate transport across the membrane.
• Nucleotide Binding Domains (NBDs): These domains bind and hydrolyze ATP to drive the transport process. ABCG proteins typically have one NBD each, requiring dimerization to form a functional transporter.

Classification and Subtypes

The ABCG subfamily includes several key members:

• ABCG1: Involved in the efflux of cholesterol and phospholipids to high-density lipoprotein (HDL) particles.
• ABCG2 (BCRP): Known as the breast cancer resistance protein, involved in multidrug resistance and the transport of xenobiotics and endogenous substrates.
• ABCG5 and ABCG8: These two proteins form a heterodimer that is crucial for the efflux of cholesterol and phytosterols from enterocytes into the intestinal lumen and from hepatocytes into bile.

Function and Biological Significance

ABCG transporters perform several essential functions:

1. Cholesterol and Lipid Transport: ABCG1, ABCG5, and ABCG8 play crucial roles in maintaining cholesterol homeostasis by mediating the efflux of cholesterol and other lipids.
2. Multidrug Resistance: ABCG2 (BCRP) contributes to the efflux of various drugs and xenobiotics from cells, conferring resistance to chemotherapy in cancer cells.
3. Sterol Homeostasis: ABCG5 and ABCG8 regulate the absorption and excretion of dietary sterols, preventing the accumulation of toxic sterol levels in the body.

Interactions

ABCG transporters interact with various molecules and proteins:

1. Lipid Molecules: They bind and transport cholesterol, phospholipids, and other lipids.
2. Other ABCG Proteins: ABCG transporters form functional dimers, either as homodimers (e.g., ABCG1) or heterodimers (e.g., ABCG5 and ABCG8).
3. Regulatory Proteins: Interactions with regulatory proteins can modulate the expression, localization, and activity of ABCG transporters.

Clinical Issues

Mutations and dysregulation of ABCG transporters are linked to several clinical conditions:

1. Sitosterolemia: Mutations in either ABCG5 or ABCG8 lead to sitosterolemia, a rare genetic disorder characterized by the accumulation of dietary sterols in the body, causing premature atherosclerosis and xanthomas.
2. Cancer: Overexpression of ABCG2 (BCRP) is associated with multidrug resistance in various cancers, complicating chemotherapy treatments.
3. Atherosclerosis: Dysregulation of ABCG1 and its role in cholesterol efflux can contribute to the development of atherosclerosis and cardiovascular diseases.

Summary

The ABCG subfamily of ATP-binding cassette transporters is essential for the transport of lipids, cholesterol, and various drugs across cellular membranes. These transporters play vital roles in maintaining lipid homeostasis, conferring multidrug resistance in cancer, and regulating sterol absorption and excretion. Mutations or dysregulation in ABCG proteins can lead to significant clinical conditions, such as sitosterolemia, cancer drug resistance, and atherosclerosis, highlighting their importance in health and disease.